Acid, Ulcers, and H. pylori

Question 0

What does low pH in the stomach induce?

Answer 0

Somatostatin release by D cells, which provides negative feedback to histamine and gastrin secretion.

Question 1

Two different second messenger systems involved in acid secretion by parietal cells?

Answer 1

Gastrin -> PLC -> etc etc. -> Ca++ influx -> more K+/H+ ATPase activity.
Histamine -> cAMP -> more K+/H+ ATPase activity.

Question 2

Which cells secrete mucus and bicarb in the stomach? What drives them to do this?

Answer 2

The surface epithelial cells (i.e. not the ones down in the pits).
Prostaglandins drive this (the ones made by COX-1).

Question 3

Is it just the acid that can damage the gastric mucosa if protective mechanism fail?

Answer 3

Nope, it’s pepsin too -> autodigestion.

Question 4

What are 3 main “aggressive factors” in ulcer formation?

Answer 4

Acid. (hypersecretion syndromes, esp ZES)
NSAIDS.
H. pylori.

Question 5

What are the “other” aggressive factors in ulcer formation that may contribute to poor healing?

Answer 5

Steroids, smoking, EtOH, bile, etc.

Question 6

Does pain with food vs. fasting really distinguish a gastric from a duodenal ulcer?

Answer 6

No.

It’s commonly said that gastric ulcers hurt while eating, duodenal ulcers hurt when fasting…

Question 7

Changing trends in ulcer prevalence?

Answer 7

Uncomplicated ulcers going down (PPIs, Tx of H. pylori).

Bleeding ulcers account for a greater proportion of those seen.

Question 8

What is Zollinger-Ellison Syndrome?

Answer 8

An islet cell tumor that secretes gastrin and isn’t inhibited by somatostatin -> very high acid levels in stomach -> ulcers.

Question 9

Why does giving a stomatostatin analogue (e.g. octreotide) work for ZES?

Answer 9

Because you’re giving it systemically.

The somatostatin made by D cells acts in a paracrine fashion, and apparently doesn’t reach the islet cell tumors of ZES.

Question 10

Diagnostic hallmark of ZES?

Answer 10

Inappropriate hypergastrinemia:

High acid, high gastrin.

Question 11

When is appropriate for gastrin to be high?

Answer 11

Any time acid is low in the stomach, such as when the patient is on PPIs.
(you have to take patients off of PPIs to really diagnose ZES, which can be risky)

Question 12

How can H. pylori cause both appropriate and inappropriate hypergastrinemia?

Answer 12

Appropriate: H. pylori can induce pangastritis that reduces acid production.
Inappropriate: inflammation can H. pylori in the antrum can cause G cell hyperplasia.

Question 13

What genetic syndrome is associated with ZES?

Answer 13

MEN-1
(Recall the 3 P’s: Parathyroid, Pituitary, and Pancreas - ZES is from the pancreas part)
(encodes Menin)

Question 14

When measuring basal acid output (BAO), is it the concentration that matters?

Answer 14

No. It’s total amount of acid (protons) made per hour.

Question 15

In idiopathic peptic ulcer disease…

Answer 15

the acid is high (esp. while fasting), and we don’t know why

Question 16

4 possible causes for hypersecretion in peptic ulcer disease?

Answer 16

Increased sensitivity of parietal cells to secretogogues.
Hypergastrinemia (basal and/or meal-based).
Insufficient inhibition (eg. by somatostatin).
Decreased bicarb secretion.

Question 17

What does H. pylori notably make? What does it do the epithelium?

Answer 17

Urease -> makes a cloud of ammonia around it that neutralizes pH.
It adheres to the epithelium, induces inflammation that reduces its integrity (which may help it get nutrients).

Question 18

How is H. pylori spread?

Answer 18

person-to-person by the fecal-oral route

Question 19

What kind of immune response does H. pylori evoke?

Answer 19

Antibodies are detectable in the serum.

Inflammation in the mucosa (gastritis).

Question 20

Does H. pylori invade the mucosa?

Answer 20

No.

Question 21

How does H. pylori change acid secretion dynamics in patients?

Answer 21

Infected patients have more gastrin-mediated acid secretion during meals.

Question 22

How does H. pylori cause hypergastrinemia?

Answer 22

By inhibiting somatostatin release.

Question 23

How is H. pylori thought to cause duodenal ulcers?

Answer 23

Hypergastrinemia -> acid -> metaplasia of the duodenal bulb to be more gastric.
H. pylori can then colonize the duodenal bulb -> inducing local loss of integrity of mucosa.
Loss of integrity + high acid -> duodenal ulcer.

Question 24

Cancers of what regions of the stomach is H. pylori infection associated with?

Answer 24

distal (corpus and antrum) cancers

Question 25

What’s one notable H. pylori virulence factor? What effect does it have?

Answer 25

CagA

CagA+ H. pylori induce more inflammatory cytokines.

Question 26

What’s a notable host polymorphism associated with greater susceptibility to H. pylori-induced cancer?

Answer 26

Polymorphisms in the IL-1R receptor (probably that make it more responsive to IL-1)

Question 27

4 environmental risk factors for gastric cancer?

Answer 27

Nitroso compounds (sushi?)
Salt
Smoking
Vitamin C deficiency

Question 28

2 ways NSAIDS affect the stomach?

Answer 28

Local, caustic effects. (not really significant)

Systemic inhibition of prostaglandin synthesis. (the problem)

Question 29

Which COX makes gastroprotective prostaglandins?

Answer 29

COX-1.
So coxibs (COX-2 inhibitors) are better for the GI tract, but cause kidney and CV problems.

Question 30

2 solutions to NSAID-induced GI problems?

Answer 30

Replace prostaglandins: misoprostol.

Give PPIs concurrently.

Question 31

What effect does H. pylori have on COX enzymes?

Answer 31

Promotes COX-2 activity.

Doesn’t affect COX-1.

Question 32

Does H. pylori infection + NSAID use = really high chance of ulcer?

Answer 32

Yes.

Question 33

4 “other” causes of ulcer?

Answer 33

Stress (burns, head injury??)
Chemotherapy
Uremia
Cancer

Question 34

Take-home point about non-ulcer causes of ulcer-like pain?

Answer 34

Rule out other causes, especially life-threatening ones like pneumonia, MI, PE, ruptured AA.